This research proposal is designed to test various aspects of the effects of the thiol agent, cysteamine (CSH) and its congeners on prolactin (PRL) secretion in the rat. Three separate but interrelated experimental approaches will be used: 1) In vitro studies will focus on the initial screening of the efficacy and specificity of a number of compounds that either have structural or functional relationships to CSH to deplete PRL from dispersed anterior pituitary (AP) cells in culture, as well as their ability to deplete PRL from bovine AP cells and rat AP tumor cells (GH(3)). 2) In Vivo studies will focus on CSH and selected compounds found active in vitro to determine their selectivity, minimal effective dose, time course, best route of administration and the drug effects when given chronically to both normal and hyperprolactinemic animals. The ability of these drugs to destroy biologically active PRL will also be tested in both animal models. 3) Finally, biochemical approaches (protein denaturation studies, gel electrophoresis and density gredient centrifugation) will be used to study the mechanism of action of CSH. In addition, the role the dopamine receptor plays in mediating the actions of these compounds will be tested. We anticipate that these studies will, 1) lay a foundation for the development of a new class of drugs that may be used clinically to treat patients with hyperprolactinemia and, 2) provide further insight into the basic cellular functions and mechanisms of the lactotrope.